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7-Dehydrocholesterol

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Sarah Shefer – One of the best experts on this subject based on the ideXlab platform.

  • 7 dehydrocholesterol dependent proteolysis of hmg coa reductase suppresses sterol biosynthesis in a mouse model of smith lemli opitz rsh syndrome
    Journal of Clinical Investigation, 2001
    Co-Authors: Barbara U Fitzky, Ashok K. Batta, Sarah Shefer, Fabian F Moebius, Hitoshi Asaoka, Heather Waagebaudet, Nobuyo Maeda, Kimberly D Kluckman, Sylvia Hiller, Thomas S. Chen
    Abstract:

    Smith-Lemli-Opitz/RSH syndrome (SLOS), a relatively common birth-defect mental-retardation syndrome, is caused by mutations in DHCR7, whose product catalyzes an obligate step in cholesterol biosynthesis, the conversion of 7-Dehydrocholesterol to cholesterol. A null mutation in the murine Dhcr7 causes an identical biochemical defect to that seen in SLOS, including markedly reduced tissue cholesterol and total sterol levels, and 30- to 40-fold elevated concentrations of 7-Dehydrocholesterol. Prenatal lethality was not noted, but newborn homozygotes breathed with difficulty, did not suckle, and died soon after birth with immature lungs, enlarged bladders, and, frequently, cleft palates. Despite reduced sterol concentrations in Dhcr7–/– mice, mRNA levels for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-controlling enzyme for sterol biosynthesis, the LDL receptor, and SREBP-2 appeared neither elevated nor repressed. In contrast to mRNA, protein levels and activities of HMG-CoA reductase were markedly reduced. Consistent with this finding, 7-Dehydrocholesterol accelerates proteolysis of HMG-CoA reductase while sparing other key proteins. These results demonstrate that in mice without Dhcr7 activity, accumulated 7-Dehydrocholesterol suppresses sterol biosynthesis posttranslationally. This effect might exacerbate abnormal development in SLOS by increasing the fetal cholesterol deficiency.

  • regulation of cholesterol biosynthetic pathway in patients with the smith lemli opitz syndrome
    Journal of Inherited Metabolic Disease, 2000
    Co-Authors: M Honda, Gerald Salen, G. S. Tint, Akira Honda, Sarah Shefer, A K Batta, Yasushi Matsuzaki, Naomi Tanaka
    Abstract:

    The Smith–Lemli–Opitz syndrome (SLOS) is a recessively inherited birth disorder caused by a defect in 7-Dehydrocholesterol (3β-hydroxysteroid) Δ7-reductase, the final enzyme in cholesterol biosynthesis. To investigate in vivo regulation of the cholesterol biosynthetic pathway in SLOS, we measured hepatic microsomal sterol concentrations and activities of several key enzymes in the pathway, including HMG-CoA synthase, HMG-CoA reductase, squalene synthase and 7-Dehydrocholesterol Δ7-reductase in liver specimens from a patient with SLOS and 11 controls. Hepatic microsomal 7-Dehydrocholesterol Δ7-reductase activity in the patient was less than 1% of the control mean, and decreased cholesterol concentration and markedly increased 7- and 8-dehydrocholesterol concentrations were observed in the patient’s microsomes. HMG-CoA synthase and squalene synthase activities in the patient were upregulated to 149% and 532%, respectively, while the activity of HMG-CoA reductase, the rate-limiting enzyme in the pathway, was reduced to 39% of the control mean. Downregulation of HMG-CoA reductase activity in SLOS was supported by measuring plasma levels of mevalonic acid, the immediate product of HMG-CoA reductase. The levels in SLOS patients (n=9) were significantly low compared with age-matched controls (n=8) (12±2 vs 28±6 nmol/L, p<0.05). These results suggest that in most SLOS patients in vivo HMG-CoA reductase is not stimulated in spite of blocked cholesterol biosynthetic pathway and reduced plasma and hepatic cholesterol concentrations.

  • 7-Dehydrocholesterol down-regulates cholesterol biosynthesis in cultured Smith-Lemli-Opitz syndrome skin fibroblasts
    Journal of lipid research, 1998
    Co-Authors: Megumi Honda, G. S. Tint, Akira Honda, Thomas S. Chen, Lien B. Nguyen, Sarah Shefer
    Abstract:

    The Smith-Lemli-Opitz syndrome (SLOS) is a com- mon birth defect-mental retardation syndrome caused by a defect in the enzyme that reduces 7-Dehydrocholesterol to cholesterol. Because of this block, patients’ plasma choles- terol levels are generally low while 7-Dehydrocholesterol con- centrations are markedly elevated. In addition, plasma total sterols are abnormally low and correlate negatively with the percent of 7-Dehydrocholesterol (r 5 2 0.65, P , 0.0001) sug- gesting that 7-Dehydrocholesterol might inhibit the activity of HMG-CoA reductase. Cultured skin fibroblasts from SLOS pa- tients grown in fetal bovine serum or for 1 day in delipidated medium contain little 7-Dehydrocholesterol (3 6 1% of total sterols) and HMG-CoA reductase activities are indistinguish- able from that measured in control cells. However, raising the 7-Dehydrocholesterol concentration to 20 6 3% of total ste- rols, equal to the mean proportion in plasma of SLOS pa- tients, by either growing cells for 1 week in delipidated me- dium or adding 20 m g/ml 7-Dehydrocholesterol directly to the cells reduced HMG-CoA reductase activities from 74 6 7 to 9 6 2 pmol/min per mg protein, or from 92 6 22 to 16 6 4 pmol/min per mg protein, respectively ( P , 0.01). In con- trast, adding 20 m g/ml cholesterol evoked a 2- to 4-fold lesser suppression of activity (39 6 8 pmol/min per mg protein, P , 0.05, vs. 7-Dehydrocholesterol). HMG-CoA synthase and LDL binding were inhibited equally by 7-Dehydrocholesterol and cholesterol. Ketaconazole prevented the down-regulation of HMG-CoA reductase by 7-Dehydrocholesterol, suggesting that an hydroxylated derivative of 7-Dehydrocholesterol may be es- pecially important in suppressing cholesterol synthesis. These results demonstrate that 7-Dehydrocholesterol, perhaps as an hydroxylated derivative(s), is a very effective feedback inhibitor of HMG-CoA reductase. —Honda, M., G. S. Tint, A. Honda, L. B. Nguyen, T. S. Chen, and S. Shefer. 7-Dehydro- cholesterol down-regulates cholesterol biosynthesis in cul- tured Smith-Lemli-Opitz syndrome skin fibroblasts. J. Lipid Res. 1998. 39: 647-657.

Gerald Salen – One of the best experts on this subject based on the ideXlab platform.

  • regulation of cholesterol biosynthetic pathway in patients with the smith lemli opitz syndrome
    Journal of Inherited Metabolic Disease, 2000
    Co-Authors: M Honda, Gerald Salen, G. S. Tint, Akira Honda, Sarah Shefer, A K Batta, Yasushi Matsuzaki, Naomi Tanaka
    Abstract:

    The Smith–Lemli–Opitz syndrome (SLOS) is a recessively inherited birth disorder caused by a defect in 7-Dehydrocholesterol (3β-hydroxysteroid) Δ7-reductase, the final enzyme in cholesterol biosynthesis. To investigate in vivo regulation of the cholesterol biosynthetic pathway in SLOS, we measured hepatic microsomal sterol concentrations and activities of several key enzymes in the pathway, including HMG-CoA synthase, HMG-CoA reductase, squalene synthase and 7-Dehydrocholesterol Δ7-reductase in liver specimens from a patient with SLOS and 11 controls. Hepatic microsomal 7-Dehydrocholesterol Δ7-reductase activity in the patient was less than 1% of the control mean, and decreased cholesterol concentration and markedly increased 7- and 8-dehydrocholesterol concentrations were observed in the patient’s microsomes. HMG-CoA synthase and squalene synthase activities in the patient were upregulated to 149% and 532%, respectively, while the activity of HMG-CoA reductase, the rate-limiting enzyme in the pathway, was reduced to 39% of the control mean. Downregulation of HMG-CoA reductase activity in SLOS was supported by measuring plasma levels of mevalonic acid, the immediate product of HMG-CoA reductase. The levels in SLOS patients (n=9) were significantly low compared with age-matched controls (n=8) (12±2 vs 28±6 nmol/L, p<0.05). These results suggest that in most SLOS patients in vivo HMG-CoA reductase is not stimulated in spite of blocked cholesterol biosynthetic pathway and reduced plasma and hepatic cholesterol concentrations.

  • Screening for abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome: Rapid determination of plasma 7-Dehydrocholesterol by ultraviolet spectrometry
    American journal of medical genetics, 1997
    Co-Authors: Akira Honda, Gerald Salen, G. S. Tint, Ashok K. Batta, Thomas S. Chen, Sarah Shefer
    Abstract:

    The Smith-Lemli-Opitz syndrome (SLOS) is a common condition caused by deficiency of 7-Dehydrocholesterol Δ 7 –reductase. The syndrome can usually be diagnosed by demonstrating markedly increased plasma concentrations of the cholesterol precursor, 7-Dehydrocholesterol. We describe a simple and rapid method for detection of plasma 7-Dehydrocholesterol by use of ultraviolet (UV) spectrometry. Lipids were extracted from plasma by addition of ethanol and n-hexane, and the n-hexane phase was directly subjected to spectrometry. The absorption maxima characteristics of 7-Dehydrocholesterol (λ max 271, 282, and 294 nm) were observed in patients’ plasma but not in controls. For quantitative measurements, absorbance at 282 nm was used. Since this absorbance is the sum of the absorbance derived from 7-Dehydrocholesterol and background absorbance, the concentrations of 7-Dehydrocholesterol in various plasma samples were quantified by subtracting estimated background absorbance at 282 nm from observed absorbance at 282 nm. The results correlated well with total (free plus esterified) 7-Dehydrocholesterol concentrations measured by gas-liquid chromatographic method. The UV spectrometric assay was sensitive enough to detect increased 7-Dehydrocholesterol in cultured skin fibroblasts from patients grown in delipidated medium. The present method will make it possible to screen plasma or fibroblasts to detect the syndrome rapidly in general clinical laboratories.

  • Rapid identification of smith-lemlip-opitz syndrome homozygotes and heterozygotes (carriers) by measurement of deficient 7-Dehydrocholesterol-Δ7-reductase activity in fibroblasts
    Metabolism: clinical and experimental, 1997
    Co-Authors: Sarah Shefer, Michael F Holick, Gerald Salen, G. S. Tint, Ashok K. Batta, Akira Honda, Megumi Honda, Susan Hauser, T. Chen, Lien B. Nguyen
    Abstract:

    Abstract To extend the enzyme deficiency in Smith-Lemli-Opitz syndrome (SLOS) to extrahepatic tissues, 7-Dehydrocholesterol-Δ 7 –reductase activity was measured in fibroblasts from 10 controls, five SLOS homozygotes, and five obligate heterozygotes. In cells grown almost to confluence in cholesterol-containing medium (4 mg/dL), the conversion of [1,2- 3 H]7-Dehydrocholesterol to cholesterol (7-Dehydrocholesterol-Δ 7 –reductase activity) was 3.8 times higher in control than in homozygote cells and 2.2 times higher than in heterozygote cells. After 24 hours’ exposure of the fibroblasts to cholesterol-deficient medium supplemented with lovastatin, 7-Dehydrocholesterol-Δ 7 –reductase activity increased twofold in controls, but did not change significantly in either heterozygous or homozygous cells. In contrast, the activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and lathosterol 5-dehydrogenase, two key enzymes that precede 7-Dehydrocholesterol-Δ 7 –reductase in the cholesterol biosynthetic pathway, and low-density lipoprotein (LDL) receptor—mediated binding were equal in control, homozygote, and heterozygote fibroblasts. Further, HMG-CoA reductase activity and LDL receptor—mediated binding increased after exposure to the cells to cholesterol-deficient medium. Fibroblast cholesterol concentrations were approximately equal, although homozygote cells contained 30 times more 7-Dehydrocholesterol. Thus, markedly reduced 7-Dehydrocholesterol-Δ 7 –reductase activity that cannot be upregulated after exposure of the cells to cholesterol-deficient medium is diagnostic for the biochemical defect in SLOS. Significantly reduced enzyme activity between the levels in controls and homozygotes without accumulation of 7-Dehydrocholesterol in fibroblasts identified heterozygotes.

G. S. Tint – One of the best experts on this subject based on the ideXlab platform.

  • regulation of cholesterol biosynthetic pathway in patients with the smith lemli opitz syndrome
    Journal of Inherited Metabolic Disease, 2000
    Co-Authors: M Honda, Gerald Salen, G. S. Tint, Akira Honda, Sarah Shefer, A K Batta, Yasushi Matsuzaki, Naomi Tanaka
    Abstract:

    The Smith–Lemli–Opitz syndrome (SLOS) is a recessively inherited birth disorder caused by a defect in 7-Dehydrocholesterol (3β-hydroxysteroid) Δ7-reductase, the final enzyme in cholesterol biosynthesis. To investigate in vivo regulation of the cholesterol biosynthetic pathway in SLOS, we measured hepatic microsomal sterol concentrations and activities of several key enzymes in the pathway, including HMG-CoA synthase, HMG-CoA reductase, squalene synthase and 7-Dehydrocholesterol Δ7-reductase in liver specimens from a patient with SLOS and 11 controls. Hepatic microsomal 7-Dehydrocholesterol Δ7-reductase activity in the patient was less than 1% of the control mean, and decreased cholesterol concentration and markedly increased 7- and 8-dehydrocholesterol concentrations were observed in the patient’s microsomes. HMG-CoA synthase and squalene synthase activities in the patient were upregulated to 149% and 532%, respectively, while the activity of HMG-CoA reductase, the rate-limiting enzyme in the pathway, was reduced to 39% of the control mean. Downregulation of HMG-CoA reductase activity in SLOS was supported by measuring plasma levels of mevalonic acid, the immediate product of HMG-CoA reductase. The levels in SLOS patients (n=9) were significantly low compared with age-matched controls (n=8) (12±2 vs 28±6 nmol/L, p<0.05). These results suggest that in most SLOS patients in vivo HMG-CoA reductase is not stimulated in spite of blocked cholesterol biosynthetic pathway and reduced plasma and hepatic cholesterol concentrations.

  • 7-Dehydrocholesterol down-regulates cholesterol biosynthesis in cultured Smith-Lemli-Opitz syndrome skin fibroblasts
    Journal of lipid research, 1998
    Co-Authors: Megumi Honda, G. S. Tint, Akira Honda, Thomas S. Chen, Lien B. Nguyen, Sarah Shefer
    Abstract:

    The Smith-Lemli-Opitz syndrome (SLOS) is a com- mon birth defect-mental retardation syndrome caused by a defect in the enzyme that reduces 7-Dehydrocholesterol to cholesterol. Because of this block, patients’ plasma choles- terol levels are generally low while 7-Dehydrocholesterol con- centrations are markedly elevated. In addition, plasma total sterols are abnormally low and correlate negatively with the percent of 7-Dehydrocholesterol (r 5 2 0.65, P , 0.0001) sug- gesting that 7-Dehydrocholesterol might inhibit the activity of HMG-CoA reductase. Cultured skin fibroblasts from SLOS pa- tients grown in fetal bovine serum or for 1 day in delipidated medium contain little 7-Dehydrocholesterol (3 6 1% of total sterols) and HMG-CoA reductase activities are indistinguish- able from that measured in control cells. However, raising the 7-Dehydrocholesterol concentration to 20 6 3% of total ste- rols, equal to the mean proportion in plasma of SLOS pa- tients, by either growing cells for 1 week in delipidated me- dium or adding 20 m g/ml 7-Dehydrocholesterol directly to the cells reduced HMG-CoA reductase activities from 74 6 7 to 9 6 2 pmol/min per mg protein, or from 92 6 22 to 16 6 4 pmol/min per mg protein, respectively ( P , 0.01). In con- trast, adding 20 m g/ml cholesterol evoked a 2- to 4-fold lesser suppression of activity (39 6 8 pmol/min per mg protein, P , 0.05, vs. 7-Dehydrocholesterol). HMG-CoA synthase and LDL binding were inhibited equally by 7-Dehydrocholesterol and cholesterol. Ketaconazole prevented the down-regulation of HMG-CoA reductase by 7-Dehydrocholesterol, suggesting that an hydroxylated derivative of 7-Dehydrocholesterol may be es- pecially important in suppressing cholesterol synthesis. These results demonstrate that 7-Dehydrocholesterol, perhaps as an hydroxylated derivative(s), is a very effective feedback inhibitor of HMG-CoA reductase. —Honda, M., G. S. Tint, A. Honda, L. B. Nguyen, T. S. Chen, and S. Shefer. 7-Dehydro- cholesterol down-regulates cholesterol biosynthesis in cul- tured Smith-Lemli-Opitz syndrome skin fibroblasts. J. Lipid Res. 1998. 39: 647-657.

  • Screening for abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome: Rapid determination of plasma 7-Dehydrocholesterol by ultraviolet spectrometry
    American journal of medical genetics, 1997
    Co-Authors: Akira Honda, Gerald Salen, G. S. Tint, Ashok K. Batta, Thomas S. Chen, Sarah Shefer
    Abstract:

    The Smith-Lemli-Opitz syndrome (SLOS) is a common condition caused by deficiency of 7-Dehydrocholesterol Δ 7 -reductase. The syndrome can usually be diagnosed by demonstrating markedly increased plasma concentrations of the cholesterol precursor, 7-Dehydrocholesterol. We describe a simple and rapid method for detection of plasma 7-Dehydrocholesterol by use of ultraviolet (UV) spectrometry. Lipids were extracted from plasma by addition of ethanol and n-hexane, and the n-hexane phase was directly subjected to spectrometry. The absorption maxima characteristics of 7-Dehydrocholesterol (λ max 271, 282, and 294 nm) were observed in patients’ plasma but not in controls. For quantitative measurements, absorbance at 282 nm was used. Since this absorbance is the sum of the absorbance derived from 7-Dehydrocholesterol and background absorbance, the concentrations of 7-Dehydrocholesterol in various plasma samples were quantified by subtracting estimated background absorbance at 282 nm from observed absorbance at 282 nm. The results correlated well with total (free plus esterified) 7-Dehydrocholesterol concentrations measured by gas-liquid chromatographic method. The UV spectrometric assay was sensitive enough to detect increased 7-Dehydrocholesterol in cultured skin fibroblasts from patients grown in delipidated medium. The present method will make it possible to screen plasma or fibroblasts to detect the syndrome rapidly in general clinical laboratories.

Forbes D. Porter – One of the best experts on this subject based on the ideXlab platform.

Akira Honda – One of the best experts on this subject based on the ideXlab platform.

  • sterols and oxysterols in plasma from smith lemli opitz syndrome patients
    The Journal of Steroid Biochemistry and Molecular Biology, 2017
    Co-Authors: William J Griffiths, Cedric H.l. Shackleton, Jonas Abdelkhalik, Peter J Crick, Michael Ogundare, Karin Tuschl, Mei Kwun Kwok, Brian W Bigger, Andrew A M Morris, Akira Honda
    Abstract:

    Smith-Lemli-Opitz syndrome (SLOS) is a severe autosomal recessive disorder resulting from defects in the cholesterol synthesising enzyme 7-Dehydrocholesterol reductase (Δ7-sterol reductase, DHCR7, EC 1.3.1.21) leading to a build-up of the cholesterol precursor 7-Dehydrocholesterol (7-DHC) in tissues and blood plasma. Although the underling enzyme deficiency associated with SLOS is clear there are likely to be multiple mechanisms responsible for SLOS pathology. In an effort to learn more of the aetiology of SLOS we have analysed plasma from SLOS patients to search for metabolites derived from 7-DHC which may be responsible for some of the pathology. We have identified a novel hydroxy-8-dehydrocholesterol, which is either 24- or 25-hydroxy-8-dehydrocholesterol and also the known metabolites 26-hydroxy-8-dehydrocholesterol, 4-hydroxy-7-Dehydrocholesterol, 3β,5α-dihydroxycholest-7-en-6-one and 7α,8α-epoxycholesterol. None of these metabolites are detected in control plasma at quantifiable levels (0.5ng/mL).

  • regulation of cholesterol biosynthetic pathway in patients with the smith lemli opitz syndrome
    Journal of Inherited Metabolic Disease, 2000
    Co-Authors: M Honda, Gerald Salen, G. S. Tint, Akira Honda, Sarah Shefer, A K Batta, Yasushi Matsuzaki, Naomi Tanaka
    Abstract:

    The Smith–Lemli–Opitz syndrome (SLOS) is a recessively inherited birth disorder caused by a defect in 7-Dehydrocholesterol (3β-hydroxysteroid) Δ7-reductase, the final enzyme in cholesterol biosynthesis. To investigate in vivo regulation of the cholesterol biosynthetic pathway in SLOS, we measured hepatic microsomal sterol concentrations and activities of several key enzymes in the pathway, including HMG-CoA synthase, HMG-CoA reductase, squalene synthase and 7-Dehydrocholesterol Δ7-reductase in liver specimens from a patient with SLOS and 11 controls. Hepatic microsomal 7-Dehydrocholesterol Δ7-reductase activity in the patient was less than 1% of the control mean, and decreased cholesterol concentration and markedly increased 7- and 8-dehydrocholesterol concentrations were observed in the patient’s microsomes. HMG-CoA synthase and squalene synthase activities in the patient were upregulated to 149% and 532%, respectively, while the activity of HMG-CoA reductase, the rate-limiting enzyme in the pathway, was reduced to 39% of the control mean. Downregulation of HMG-CoA reductase activity in SLOS was supported by measuring plasma levels of mevalonic acid, the immediate product of HMG-CoA reductase. The levels in SLOS patients (n=9) were significantly low compared with age-matched controls (n=8) (12±2 vs 28±6 nmol/L, p<0.05). These results suggest that in most SLOS patients in vivo HMG-CoA reductase is not stimulated in spite of blocked cholesterol biosynthetic pathway and reduced plasma and hepatic cholesterol concentrations.

  • 7-Dehydrocholesterol down-regulates cholesterol biosynthesis in cultured Smith-Lemli-Opitz syndrome skin fibroblasts
    Journal of lipid research, 1998
    Co-Authors: Megumi Honda, G. S. Tint, Akira Honda, Thomas S. Chen, Lien B. Nguyen, Sarah Shefer
    Abstract:

    The Smith-Lemli-Opitz syndrome (SLOS) is a com- mon birth defect-mental retardation syndrome caused by a defect in the enzyme that reduces 7-Dehydrocholesterol to cholesterol. Because of this block, patients’ plasma choles- terol levels are generally low while 7-Dehydrocholesterol con- centrations are markedly elevated. In addition, plasma total sterols are abnormally low and correlate negatively with the percent of 7-Dehydrocholesterol (r 5 2 0.65, P , 0.0001) sug- gesting that 7-Dehydrocholesterol might inhibit the activity of HMG-CoA reductase. Cultured skin fibroblasts from SLOS pa- tients grown in fetal bovine serum or for 1 day in delipidated medium contain little 7-Dehydrocholesterol (3 6 1% of total sterols) and HMG-CoA reductase activities are indistinguish- able from that measured in control cells. However, raising the 7-Dehydrocholesterol concentration to 20 6 3% of total ste- rols, equal to the mean proportion in plasma of SLOS pa- tients, by either growing cells for 1 week in delipidated me- dium or adding 20 m g/ml 7-Dehydrocholesterol directly to the cells reduced HMG-CoA reductase activities from 74 6 7 to 9 6 2 pmol/min per mg protein, or from 92 6 22 to 16 6 4 pmol/min per mg protein, respectively ( P , 0.01). In con- trast, adding 20 m g/ml cholesterol evoked a 2- to 4-fold lesser suppression of activity (39 6 8 pmol/min per mg protein, P , 0.05, vs. 7-Dehydrocholesterol). HMG-CoA synthase and LDL binding were inhibited equally by 7-Dehydrocholesterol and cholesterol. Ketaconazole prevented the down-regulation of HMG-CoA reductase by 7-Dehydrocholesterol, suggesting that an hydroxylated derivative of 7-Dehydrocholesterol may be es- pecially important in suppressing cholesterol synthesis. These results demonstrate that 7-Dehydrocholesterol, perhaps as an hydroxylated derivative(s), is a very effective feedback inhibitor of HMG-CoA reductase. —Honda, M., G. S. Tint, A. Honda, L. B. Nguyen, T. S. Chen, and S. Shefer. 7-Dehydro- cholesterol down-regulates cholesterol biosynthesis in cul- tured Smith-Lemli-Opitz syndrome skin fibroblasts. J. Lipid Res. 1998. 39: 647-657.